The present study is directed toward an understanding of the molecular basis of the interaction between oral bacteria and specific salivary proteins. The result of this interaction is the aggregation of bacteria and the enhanced adsorption of certain bacteria onto the tooth surface. Bacteria on teeth become embedded in a protein and polysaccharide matrix and, indeed, bacteria come to exist in extremely high concentrations in the resulting dental plaque. The role of plaque in causing dental disease is well documented. Proposals are outlined for the investigation of the kinetic parameters of the protein-bacteria interaction and for the purification of the different salivary aggregating factors and bacterial surface receptors. The purified materials will be analyzed by various means and determinations will be made of the reactive sites on the molecules. The molecular forces that operate at these sites must be made clear if one is to understand the nature of plaque. From these results and from the methods used may come a new rationale for the prevention of caries and periodontal disease.